Resistance to anti-PD-1/PD-L1 immune checkpoint blockade continues to be a critical challenge undermining its therapeutic efficacy in clinical applications. Most of the resistance mechanisms characterized to date have predominantly involved external factors beyond PD-L1. Here, we unexpectedly discovered that PD-L1 itself possesses E3 ubiquitin ligase activity to induce β2m ubiquitylation and subsequent degradation, which notably reduces MHC-I levels on the surface of tumor cells and antigen-presenting cells, thereby contributing to tumor cell evasion of recognition by CD8+ T cells and ultimately resulting in resistance to anti-PD-1/PD-L1 immunotherapy, particularly in tumors with low basal β2m expression. Disrupting the E3 ubiquitin ligase activity of PD-L1 or interfering with the PD-L1–β2m interaction dramatically enhanced the sensitivity of tumor cells to PD-L1 blockade therapy. Our study reveals a previously unknown function of PD-L1 in the immune evasion of tumor cells, expanding our understanding of intrinsic resistance mechanisms to immune checkpoint blockade therapy.

BACKGROUND:Thyroid nodule ultrasound (US) images and their features are of great importance in thyroid nodule diagnosis and can be helpful for radiologists' clinical decision making. The aim was to evaluate whether an artificial intelligence (AI)-assisted system can accurately characterize thyroid nodule US features and assist radiologists in diagnosing thyroid cancer. METHODS:The AI-assisted system (MDT-TC) was trained and internally validated on B-mode US images from 7204 lesions in 6884 patients in Southwest Hospital. The model performance was validated using 3 independent external validation cohorts. RESULTS:Echogenicity (ECH) and shape (SHA) are features of high importance for model recognition, and these features lead to excellent model performance. The model achieved up to 87.56% accuracy in determining ECH attributes and 69.21% in identifying shape categories. The area under the receiver operating characteristic curve (AUC) of the internal validation cohort and 3 independent external validation cohorts for MDT-TC were 0.951, 0.837, 0.816, and 0.871, respectively. The sensitivity values were 98.7%, 91.2%, 90.3%, and 85.6%, respectively. The AUC for the accurate diagnosis of radiologists with MDT-TC assistance was significantly higher than that of radiologists without MDT-TC assistance (P < .001). In addition, the AUC for the accurate diagnosis of junior doctors with MDT-TC assistance was significantly higher than that for those without (P < .01). CONCLUSION:MDT-TC incorporates radiomic features extracted from thyroid lesion US images and can significantly improve the diagnostic performance of radiologists. This result was particularly strong for junior doctors. Therefore, our data support the idea that MDT-TC can help to identify patients with thyroid cancer and could greatly benefit clinical practice.

Esophageal squamous cell carcinoma (ESCC) is a lethal disease due to its high invasiveness and metastatic potential, but the mechanisms underlying its progression remain unclear. Although high levels of Toll-like receptor 9 (TLR9) are correlated with poor survival in ESCC, the function and regulation of TLR9 in ESCC cells remain unclear. In this study, we analyzed an ESCC tissue cohort and the TCGA_ESCC database and used mass spectrometry and RNA sequencing to explore mechanisms underlying TLR9 function, which were confirmed by in vitro and in vivo experiments. We found that TLR9 promoted cell motility and conferred resistance to cisplatin in ESCC cells. Mechanistically, TLR9 led to activation of epithelial–mesenchymal transition (EMT) via the NF-κB signaling pathway. Proteomic analysis showed that TLR9 agonist treatment mimicked the effects of TLR9 overexpression on EMT in ESCC cells, whereas TLR9 inhibitor suppressed TLR9-induced activation of EMT. Analyses on the TCGA_ESCC database and multiple miRNA databases revealed positive and negative regulation of TLR9 mRNA levels by SPI1 and miR-574-5p, respectively, which revealed two novel regulation routes for TLR9: one is SPI1-mediated positive regulation, and the other is cisplatin/IRF1/miR-574-5p-mediated negative regulation. The combination of cisplatin with a TLR9 inhibitor significantly improved survival in tumor-bearing mice. Our work provided novel insights into TLR9 in ESCC, suggesting that TLR9 could be a biomarker to predict the prognosis of ESCC patients as well as evaluate the response of ESCC patients to cisplatin treatment. Therefore, targeting TLR9 might represent a potential therapeutic strategy for ESCC treatment.

Background Selection between open thyroidectomy (OT) and minimally invasive (endoscopic/robotic) thyroidectomy for patients with thyroid cancer has been a subject of considerable debate. Comprehensive analysis of the short-term outcomes of endoscopic thyroidectomy (ET), robotic-assisted thyroidectomy (RT) and open thyroidectomy (OT) for thyroid cancer using a large-scale dataset is important. Methods This cohort study evaluated the outcomes of patients receiving ET, RT or OT for thyroid cancer from January 1, 2003, to December 31, 2022. Propensity score matching (PSM) was performed among patients treated with ET, RT or OT to balance covariates distribution. This study involved single-institution patients (aged 18–70) who had undergone ET, RT or OT for thyroid cancer. Results The study included 11,066 thyroid cancer patients (OT group– mean (SD) age: 42.45 (10.84) years; ET group– mean (SD) age: 36.75 (9.32) years and RT group– mean (SD) age: 40.27 (10.42) years). After PSM for demographic and clinical characteristics, 908 matched pairs of patients (ET vs OT) and 1480 matched pairs (RT vs OT) were included for further analysis. Complication analysis revealed that RT was associated with a lower rate of transient hypoparathyroidism (339 (22.9%) vs 687 (46.4%); P < 0.001), a lower rate of permanent hypoparathyroidism (4 (0.3%) vs 16 (1.1%); P = 0.012) and a lower rate of transient recurrent laryngeal nerve injury (63 (4.3%) vs 89 (6.0%); P = 0.037). Conclusion This cohort study analyzed the short-term outcomes between ET, RT and OT in a large sample of patients with thyroid cancer over a period of two decades. PSM provided a comparable cohort, and the results suggested the advantage of RT, which reduced Clavien–Dindo grade Ⅰ complications in the surgical treatment of thyroid cancer.

Background:Polyacrylamide hydrogel (PAAG) injection has been used for breast augmentation, enjoying popularity for nearly 20 years in the late 20th century. However, numerous complications were gradually observed in the years following the injection, including breast lumps, inflammation, firmness, and migration. Distant migration of breast fillers is relatively rare. Case Description:This case report describes the treatment of a patient who experienced complications due to distant migration of fillers after PAAG injection for breast augmentation. The patient had a right-sided lumboabdominal mass measured approximately 35 cm × 20 cm, with asymmetrical breasts and a significantly smaller right-side breast compared to the left-side. The patient underwent surgery to extract the breast augmentation material from the lumboabdominal wall and breasts, followed by a robot-assisted excision of the lumboabdominal wall capsule and removal of residual breast augmentation agent in breasts, and immediate prosthetic breast reconstruction. Postoperative abdominal scarring was strategically concealed in an area that can be covered by pants, and the breast incisions were hidden under the axillary regions. The patient was satisfied with the abdominal scarring and reconstructed breasts. Conclusions:Robot-assisted excision of the lumboabdominal wall capsule is a feasible technique for extensive migration of breast fillers in the future. Further follow-up is needed to determine the long-term effects.

Objective:To investigate and compare the efficacy and safety of unilateral axillary bilateral areola（UABA）approach and Da Vinci robotic surgery in the treatment of low-risk thyroid cancer with unilateral adenolotomy and unilateral central lymph node dissection.Methods:The clinical data of 124 patients with thyroid cancer who underwent unilateral adenolotomy plus unilateral central lymph node dissection through the UABA approach from January 2019 to December 2019 were retrospectively analyzed. They were divided into two groups according to different operation methods：61 cases（robot group）and 63 cases（endoscopic group）. SPSS 25.0 software was used for statistical analysis. Perioperative indicators were expressed as（mean ± standard）deviation，and t test was used. Age，tumor size and number of central lymph nodes were represented by M（QR），and Mann-Whitney U test was used. Gender，tumor location，number of transplanted parathyroid glands，postoperative hypocalcemia and transient hypoparathyroidism were expressed by frequency and percentage using χ2 test. P<0.05 was statistically significant.Results:The operative time and the number of parathyroid transplantation cases in the robot group were less than those in the endoscopic group（P<0.001）. The number of central lymph nodes in the robot group was significantly higher than that in the endoscopic group［8（6，12）vs. 6（3，8），P=0.021］. There was no significant difference in the number of metastatic lymph nodes and the incidence of postoperative complications between 2 groups（P > 0.05）.Conclusions:Unilateral lobotomy via UABA approach and robotic surgery plus single central region dissection are both safe and effective for low-risk thyroid cancer，and robotic surgery can better preserve parathyroid glands in situ.

Background:Early diagnosis of breast cancer has always been a difficult clinical challenge. We developed a deep-learning model EDL-BC to discriminate early breast cancer with ultrasound (US) benign findings. This study aimed to investigate how the EDL-BC model could help radiologists improve the detection rate of early breast cancer while reducing misdiagnosis. Methods:In this retrospective, multicentre cohort study, we developed an ensemble deep learning model called EDL-BC based on deep convolutional neural networks. The EDL-BC model was trained and internally validated on B-mode and color Doppler US image of 7955 lesions from 6795 patients between January 1, 2015 and December 31, 2021 in the First Affiliated Hospital of Army Medical University (SW), Chongqing, China. The model was assessed by internal and external validations, and outperformed radiologists. The model performance was validated in two independent external validation cohorts included 448 lesions from 391 patients between January 1 to December 31, 2021 in the Tangshan People's Hospital (TS), Chongqing, China, and 245 lesions from 235 patients between January 1 to December 31, 2021 in the Dazu People's Hospital (DZ), Chongqing, China. All lesions in the training and total validation cohort were US benign findings during screening and biopsy-confirmed malignant, benign, and benign with 3-year follow-up records. Six radiologists performed the clinical diagnostic performance of EDL-BC, and six radiologists independently reviewed the retrospective datasets on a web-based rating platform. Findings:The area under the receiver operating characteristic curve (AUC) of the internal validation cohort and two independent external validation cohorts for EDL-BC was 0.950 (95% confidence interval [CI]: 0.909-0.969), 0.956 (95% [CI]: 0.939-0.971), and 0.907 (95% [CI]: 0.877-0.938), respectively. The sensitivity values were 94.4% (95% [CI]: 72.7%-99.9%), 100% (95% [CI]: 69.2%-100%), and 80% (95% [CI]: 28.4%-99.5%), respectively, at 0.76. The AUC for accurate diagnosis of EDL-BC (0.945 [95% [CI]: 0.933-0.965]) and radiologists with artificial intelligence (AI) assistance (0.899 [95% [CI]: 0.883-0.913]) was significantly higher than that of the radiologists without AI assistance (0.716 [95% [CI]: 0.693-0.738]; p < 0.0001). Furthermore, there were no significant differences between the EDL-BC model and radiologists with AI assistance (p = 0.099). Interpretation:EDL-BC can identify subtle but informative elements on US images of breast lesions and can significantly improve radiologists' diagnostic performance for identifying patients with early breast cancer and benefiting the clinical practice. Funding:The National Key R&D Program of China.

Background: To compare the efficacy and safety of unilateral axilla-bilateral areola (UABA) approach for robot-assisted thyroidectomy with conventional open surgery in thyroid cancer patients. Methods: The clinicopathological features and surgical outcomes of 194 thyroid cancer patients treated by robotic surgery using the UABA approach and 217 patients treated by open surgery in our department from January 2017 to August 2018 were analysed and compared. Results: The operation time was longer in the robotic group than in the open surgery group. The patients' satisfaction with neck appearance was higher in the robotic group than in the open surgery group (91.2% vs. 21.6%, P<0.01). After total thyroidectomy and central lymph node dissection, the incidence of postoperative transient hypoparathyroidism and postoperative permanent hypoparathyroidism in the open surgery group was 29.7% (44/148) and 6.8% (10/148), higher than that [17.9% (27/151) and 2.0% (3/151)] in the robotic group (P<0.05 respectively). No significant difference was observed in the number of dissected lymph nodes or postoperative serum thyroglobulin (TG) levels or incidence of transient or permanent hoarseness of voice between the two groups. No recurrence or metastasis was found. Conclusions: Compared with open surgery, UABA robotic surgery preserved the neck appearance and effectively reduced hypoparathyroidism by super-meticulous capsular dissection (SMCD).

BACKGROUND:Triple-negative breast cancer (TNBC) is one of the most aggressive subtypes of breast cancer with poorest clinical outcomes. Patients of childbearing age have a higher probability of TNBC diagnosis, with more demands on maintenance and restoration of physical and psychosocial function. This study aimed to design effective and comprehensive nomograms to predict survival in these patients.METHODS:We used the SEER database to identify patients with TNBC aged between 18 and 45 and randomly classified these patients into a training (n=2,296) and a validation (n=2,297) cohort. Nomograms for estimating overall survival (OS) and breast cancer-specific survival (BCSS) were generated based on multivariate Cox proportional hazards models and competing-risk models in the training cohort. The performances of the nomograms were quantified in the validation cohort using calibration curves, time-dependent receiver operating characteristic (ROC) curves and Harrell's concordance index (C-index).RESULTS:A total of 4,593 TNBC patients of childbearing age were enrolled. Four prognostic factors for OS and six for BCSS were identified and incorporated to construct nomograms. In the validation cohort, calibration curves showed excellent agreement between nomogram-predicted and actual survival data. The nomograms also achieved relatively high Harrell's C-indexes and areas under the time-dependent ROC curves for estimating OS and BCSS in both training and validation cohorts.CONCLUSIONS:Independent prognostic factors were identified, and used to develop nomograms to predict OS and BCSS in childbearing-age patients with TNBC. These models could enable individualized risk estimation and risk-adapted treatment for these patients.

Purpose Osteoarthritis is one of the most common chronic diseases nowadays, and can cause serious physical illness and economic burden. Cartilage degeneration is one of primary reasons for osteoarthritis, but there were not thorough studies on cartilage lesions. Methods miR-338-5p and miR-4776-3p were overexpressed and knocked down in SW1353 cells. Dual luciferase assay is used to detect the binding of miR-338-5p, miR-4776-3p and SOX6 . The expression of MMP13 , TNFA , IL6 , MCP1 , PARP, Runx2 , ALP , OPN , WNT4 , WNT16 , TRACP and CTSK was quantified by qPCR. And the expression of WNT4 at the protein level was quantified by WB. Results In this study, we found miR-338-5p and miR-4776-3p showed significantly high expression on cartilage in osteoarthritis through bioinformatics methods, and verified miR-338-5p and miR-4776-3p can improve catabolism, and trigger biological processes such as inflammation and apoptosis. Meanwhile we validated miR-338-5p and miR-4776-3p may play negative regulation in the process of bone biology. Conclusions Our study showed that miR-338-5p and miR-4776-3p can be regarded as medium of articular cartilage degeneration, and it provided new biomarker of early diagnosis in cartilage disease and osteoarthritis.

Abstract Objective The aim of this study was to validate the predictors of peropertive computed tomography imaging parameters for sternotomy in patients with substernal goiter.Methods We retrospectively reviewed complete clinical and computed tomography data of 37 patients who had substernal goiter and underwent surgery from January 2010 to February 2019. The patients were divided into two groups based on whether or not underwent sternotomy surgery. The maximum length and width, length behind sternum of tumors were measured on preoperative computed tomography images, the volume above and below sternum, and total volume of tumors was calculated. Logstic regression model and receiver operating characteristic curve analysis were performed to identify siginificant predictors associated with sternotomy.Results Out of a total of 37 patients, 4 patients (10.8%) underwent sternotomy. The length, width and length behind sternum, as well as the volume below sternum and the total volume of tumors were significantly greater in patients with sternotomy compared to those without sternotomy (all P<0.05). The length behind sternum (OR 1.152, 95% CI: 1.012-1.312, P = 0.033) of tumors was the simple and convenient predictor for sternotomy in substernal goiter. The optimal cut-off value of length behind sternum was 46.7 mm (area under the curve: 0.962, 95% CI: 0.896-1.028, P ≤ 0.01), and the sensitivity and specificity was 100% and 87.9%, respectively.Conclusion Computed tomography examination plays an important role in determining the surgery need for substernal goiter. The length behind sternum of tumor is a convenient and independent predictor of sternotomy for substernal goiter.

BACKGROUND:Lymph node metastasis of triple-negative breast cancer (TNBC) is essential in treatment strategy formulation. This study aimed to build a nomogram that predicts lymph node metastasis in patients with TNBC.MATERIALS AND METHODS:A total of 28,966 TNBC patients diagnosed from 2010 to 2017 in the Surveillance, Epidemiology and End Results (SEER) database were enrolled, and randomized 1:1 into the training and validation sets, respectively. Univariate and multivariate logistic regression analysis were applied to identify the predictive factors, which composed the nomogram. The receiver operating characteristic curves showed the efficacy of the nomogram.RESULT:Multivariate logistic regression analyses revealed that age, race, tumor size, tumor primary site, and pathological grade were independent predictive factors of lymph node status. Integrating these independent predictive factors, a nomogram was successfully developed for predicting lymph node status, and further validated in the validation set. The areas under the receiver operating characteristic curves of the nomogram in the training and validation sets were 0.684 and 0.689 respectively, showing a satisfactory performance.CONCLUSION:We constructed a nomogram to predict the lymph node status in TNBC patients. After further validation in additional large cohorts, the nomogram developed here would do better in predicting, providing more information for staging and treatment, and enabling tailored treatment in TNBC patients.

Platinum-based regimens have been routinely used in the clinical treatment of patients with esophageal squamous cell carcinoma (ESCC). However, administration of these drugs is frequently accompanied by drug resistance. Revealing the underlying mechanisms of the drug resistance and developing agents that enhance the sensitivity to platinum may provide new therapeutic strategies for the patients. In the present study, we found that the poor outcome of ESCC patients receiving platinum-based regimens was associated with co-expression of Shh and Sox2. The sensitivity of ESCC cell lines to cisplatin was related to their activity of Shh signaling. Manipulating of Shh expression markedly changed the sensitivity of ESCC cells to platinum. Continuous treatment with cisplatin resulted in the activation of Shh signaling and enhanced cancer stem cell-like phenotypes in ESCC cells. Dihydroartemisinin (DHA), a classic antimalarial drug, was identified as a novel inhibitor of Shh pathway. Treatment with DHA attenuated the cisplatin-induced activation of the Shh pathway in ESCC cells and synergized the inhibitory effect of cisplatin on proliferation, sphere and colony formation of ALDH-positive ESCC cells in vitro and growth of ESCC cell-derived xenograft tumors in vivo . Taken together, these results demonstrate that the Shh pathway is an important player in cisplatin-resistant ESCC and DHA acts as a promising therapeutic agent to sensitize ESCC to cisplatin treatment.

Graves' disease is the most common cause of hyperthyroidism in children. The surgery treatment for children Graves' disease with huge goiter is high risk and controversial. A 14-year-old girl suffered Graves' disease with huge goiter and failed to the antithyroid drug therapy for nearly 4 years was surgically treated with total thyroidectomy. The excised thyroid weighed 449.1 g and heavier than any excised children goiter reported so far. After operation, the patient's symptoms of Graves' disease were significantly improved without any complication, including normal basal metabolic rate, relieved exophthalmia and euthyroidism. So, a children Graves' disease with huge goiter was cured by total thyroidectomy, suggesting that a total/near-total thyroidectomy is a good option for children Graves' disease with huge goiter.

Objective To investigate the anti-adhesion effect of anti-adhesion film in robotic thyroid cancer surgery. Methods We retrospectively analyzed the clinical data and treatment outcomes of 452 patients who underwent Da Vinci robotic surgery for thyroid cancer between January, 2016 and December, 2018.In 228 of the patients, anti-adhesion film (absorbable medical film) was placed on the trachea before thyroid resection and dissection of the lymph nodes (test group); the other 224 patients underwent identical surgical procedures but without the use of the anti-adhesion film (control group). Results The scores for swallowing discomfort were significantly lower in the test group than in the control group at 3 and 6 months after the operation.Subgroup analysis showed that in the patients receiving unilateral thyroidectomy, the scores for swallowing discomfort did not differ significantly between the 2 groups at 3, 6, and 12 months postoperatively.In patients receiving total thyroidectomy, the scores were significantly lower in the test group than in the control group at 3 months (P=0.00) and 6 months (P=0.001), and the incidence of swallowing discomfort (either mild or severe) was also significantly lower in the test group at 3 months (74.6% vs 83.6%, P=0.004) and 6 months (24.2% vs 40.9%, P=0.006) after the operation.No significant differences were found in the incidences of postoperative hoarseness and hypoparathyroidism, drainage volume, or the length of hospital stay between the 2 groups. Conclusion The use of absorbable medical film during robotic total thyroidectomy for thyroid cancer can effectively reduce neck soft tissue adhesion, lower the incidence of postoperative swallowing discomfort, and improve postoperative quality of life of the patients.

目的 探讨乳腺癌术后一期假体重建患者免除乳房假体区域放射治疗对并发症及复发、转移的影响.方法 依据纳入、排除标准,选取2012年1月至2014年12月在陆军军医大学第一附属医院乳腺甲状腺外科确诊为乳腺癌,且行根治性切除加假体植入一期乳房重建术后放射治疗的95例患者进行回顾性研究.所有患者中,接受乳房假体区域加淋巴结引流区域放射治疗者56例(对照组),免除乳房假体区域放射治疗而仅接受淋巴结引流区域放射治疗者39例(试验组).每例患者经过5年以上的随访.对比分析2组患者放射治疗相关并发症(放射性皮肤损伤、放射性肺炎、包膜挛缩和假体取出),以及肿瘤局部复发和远处转移的情况.放射治疗相关并发症发生率、肿瘤局部复发率及远处转移率的比较,采用χ2检验或Fisher确切概率检验.结果 对照组56例患者中,发生5例(8.9％)放射性皮肤损伤,2例(3.6％)放射性肺炎,5例(8.9％)放射治疗引起的包膜挛缩(Ⅱ级和Ⅲ级各2例,Ⅳ级1例),共导致2例(3.6％)假体取出,而试验组39例患者中,只发生1例(2.6％)放射性皮肤损伤;2组相比,放射性皮肤损伤、放射性肺炎、放射治疗引起的包膜挛缩和假体取出发生率的差异均无统计学意义(P=0.395、0.511、0.076、0.511).对照组共有12例(21.4％,12/56)患者发生放射治疗相关并发症,试验组仅1例(2.6％,1/39)患者发生放射治疗相关并发症,2组相比,差异有统计学意义(χ2=6.926,P=0.008).中位随访66个月(范围:60～81个月),对照组发生局部复发4例(7.1％,4/56)和远处转移5例(8.9％,5/56),试验组局部复发和远处转移均为3例(7.7％,3/39),2组比较,差异均无统计学意义(P=0.999、0.999).结论 对于接受乳腺癌根治性切除术后一期假体重建的患者,免除乳腺假体区域放射治疗不影响其疗效,同时可以减少放射治疗相关并发症,改善患者术后生活质量.

Triple negative breast cancer (TNBC) is a highly aggressive cancer and lack of targeting therapies.It is believed that the breast cancer stem cells (BCSCs) are responsible for the aggressive characteristics of TNBC.Hence, developing BCSC-targeting agents may provide new therapeutic strategies for the patients.Huaier polysaccharide (HP), an active ingredient extracted from the mushroom Trametes robiniophila Murr, has been widely used in clinical anti-cancer treatments in China.Here we demonstrated that HP could target BCSCs in TNBC cells, resulting in decreased mammosphere formation, downregulated expression of stem-related genes and reduced proportion of aldehyde dehydrogenase positive cells in vitro, and inhibited xenograft tumor formation in vivo.Mechanically, HP markedly reduced the expression of estrogen receptor α-36 (ERα-36), a recently identified subtype of estrogen receptor α, and attenuated ERα-36-mediated activation of AKT/β-catenin signaling in ERα-36 high TNBC cells.This study provides a new insight into the mechanism of HP on BCSC-targeting therapy and new ideas for comprehensive treatment strategies for TNBC.

Serum biomarkers for monitoring the efficacy of neoadjuvant chemotherapy in triple-negative breast cancer patients have not been established. We found that serum levels of sPD-L1 and sPD-1 were increased with tumor stages in triple-negative breast cancer patients with higher tumor stage and were significantly reduced after neoadjuvant chemotherapy in patients with positive outcomes. Background: Neoadjuvant chemotherapy (NAC) is widely administered in the primary treatment of triple-negative breast cancer (TNBC). However, serum biomarkers for evaluating or monitoring the curative efficacy of NAC have not been established. Accumulating data have shown that soluble programmed death 1 (sPD-1) and its ligand (sPD-L1) might be potential biomarkers for evaluating the curative efficacy of chemotherapy and patient prognosis in several cancers but not yet in breast cancer. Patients and Methods: Blood specimens were obtained from 66 TNBC patients who received NAC and 59 healthy women. The serum concentrations of sPD-1 and sPD-L1 were measured by enzyme-linked immunosorbent assay. Results: Compared to healthy women, the serum concentration of sPD-1 was significantly elevated in TNBC patients before NAC (549.3 +/- 58.76 pg/mL vs. 379.2 +/- 17.30 pg/mL, P = .007), but there was only an increase tendency for sPD-L1 (227.7 +/- 23.99 pg/mL vs. 195.0 +/- 8.49 pg/mL, P = .22). The serum levels of sPD-1 and sPD-L1 before NAC in TNBC patients increased with tumor stage (P = .038 and .030, respectively). Patients who experienced complete or partial remission after NAC had significantly decreased serum levels of sPD-1 and sPD-L1 compared to patients with a poor response to NAC (P = .019 and .021, respectively). Conclusion: Serum levels of sPD-1 and sPD-L1 could be used as noninvasive biomarkers for evaluating the malignancy of TNBC before NAC and for predicting the NAC response in TNBC patients. (C) 2019 Published by Elsevier Inc.

Purpose: Meticulous capsular dissection can preserve the function of the parathyroid gland in most patients, but it is difficult to identify and preserve the subcapsular parathyroid gland. We performed in-situ preservation of the subcapsular parathyroid gland during robotic radical thyroidectomy using super-meticulous capsular dissection, and evaluated its effect on postoperative parathyroid function. Methods: A 45-year-old woman was admitted with bilateral thyroid nodules. Color Doppler ultrasound demonstrated a 7 x 7 x 6 mm hypoechoic area in the middle and inferior part of the right lobe and 3 x 3 x 3 mm hypoechoic nodule in the middle part of the left lobe. She was diagnosed with right thyroid papillary cancer by fine-needle aspiration. Robotic bilateral thyroidectomy plus right central lymph node dissection was performed. During the left thyroidectomy, we found that the left inferior parathyroid gland was just under the true capsule. Subsequently, the super-meticulous capsular dissection was performed for in-situ preservation of the parathyroid gland. Results: The patient's serum parathyroid hormone concentration was 43.77 pg/ml before and 37.98 pg/ml after surgery (normal: 15-65 pg/ml). Her blood calcium level was 2.21 mmol/1 before and 2.18 mol/l after surgery (normal: 2.10-2.65 mmol/l). Conclusions: The super-meticulous capsular dissection, which could cut through the true capsule to identify subcapsular parathyroid and protect its anatomic structure as well as blood supply, is recommend for in-situ preservation of subcapsular parathyroid gland during robotic radical thyroidectomy.

Background: For a long period of time, the Mediterranean diet (MD) has been regarded by many as a very healthy and balanced daily diet that may be related to the incidences of many types of cancer. However, the association between an MD and breast cancer risk remains inconsistent even though many studies about the topic have been conducted. Hence, we performed a meta-analysis to evaluate the relationship between an MD and breast cancer risk. Methods: We searched PubMed, Medline, and EMBASE for relevant articles published earlier than May 2017. “Mediterranean diet” combined with “breast cancer” and “breast carcinoma” were used as search terms. The combined relative risk (RR) and corresponding 95% confidence interval (CI) were used to evaluate the association between an MD and breast cancer risk. Results: A total of 18 articles were included in our meta-analysis; the studies spanned 11 years, ranging from 2006 to May 2017. Ten cohort and 8 case-control studies were included. Seven studies analyzed breast cancer incidence separately in premenopausal and postmenopausal women, whereas 6 studies were performed only in postmenopausal women, for a total of 13 analyses in postmenopausal women and 7 analyses among premenopausal women. Our meta-analysis revealed a significant and inverse association of the MD and breast cancer risk (RR: 0.92, 95% CI: 0.86, 0.99). Stratification analysis by study design and menopause status revealed a significant inverse association between the MD and breast cancer risk in case-control studies (RR: 0.85, 95% CI: 0.73, 0.99) and postmenopausal women (RR: 0.91, 95% CI: 0.85, 0.97) but not in cohort studies and premenopausal women. Conclusions: Our meta-analysis revealed that an MD is significantly associated with a reduction of breast cancer risk in women, especially postmenopausal women. The MD can be suggested to women, especially postmenopausal women, as a healthy diet to reduce breast cancer risk.